EZH2 enhances the invasive capability of renal cell carcinoma cells via activation of STAT3

Mol Med Rep. 2018 Mar;17(3):3621-3626. doi: 10.3892/mmr.2017.8363. Epub 2017 Dec 27.

Abstract

The enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) gene has been recognized to be a proto‑oncogene and to be linked to human malignancies. However, the additional functions of EZH2 in renal cell carcinoma (RCC) are not completely understood. In the present study, a possible role of EZH2 in RCC was identified. EZH2 was demonstrated to promote the cell proliferation and invasion potential of 769‑P cells, and inhibition of EZH2 was demonstrated to prevent these two processes in 786‑O cells. Mechanically, EZH2 was demonstrated to increase the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and upregulate 72 kDa type IV collagenase (MMP‑2) expression. When cells were treated with small interfering RNA targeting STAT3 or Stattic, a specific inhibitor of STAT3, the invasive ability of the cells was decreased and downregulation of MMP‑2 was observed. Based on these results, in the present study it was hypothesized that EZH2 may serve a critical role in the progression of RCC. Its ability to facilitate invasion makes EZH2 a promising target for the management of advanced RCC.

Keywords: enhancer of zeste homolog 2; signal transducer and activator of transcription 3; metastasis; renal cell carcinoma.

MeSH terms

  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Enhancer of Zeste Homolog 2 Protein / antagonists & inhibitors
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Humans
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Matrix Metalloproteinase 2 / metabolism
  • Phosphorylation
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*

Substances

  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Matrix Metalloproteinase 2